The interferons are proteins which are essential for host defense against viral infection, modulate the immune response and may regulated cell growth rates. One of the mediators of interferon action is a (2'-5') oligoadenylate-dependent endoribonuclease (RNase L) which is responsible for the observed degradation of viral mRNA seen in virus-infected, interferon-treated cells. In the proposed research, RNase L will be purified and characterized with regard to its activation by (2'-5') oligoadenylates, its substrate specificity and its sensitivity to sulfhydryl reagents. Antibody to RNase L will be produced and used to facilitate purification and functional characterization. The amino acid sequence of RNase L will be determined. The gene encoding RNase L will be obtained, its chromosomal location determined, the intron-exon structure and DNA sequence of the gene determined. Portions of the gene required for regulation of its expression will be identified. Increased knowledge of RNase L and the gene encoding it will increase scientific understanding of enzyme regulation and regulation of gene expression. This knowledge may be of value to medical researchers developing new treatments for cancer, viral disease, or immunological disorders. The candidate will devote 100% effort to the research project and research related activities. In addition to participating directly in the research project, the candidate will devote additional time to learning advanced methodologies, conducting collaborative research, and attending scientific meetings. In order to devote full time to research, the candidate will be relieved of teaching and service responsibilities not directly related to research. Facilities required for successful completion of this research project are available in the candidates laboratory and elsewhere at Arizona State University. By concentrating full time on research, the candidate will be able to achieve a level of productivithy and creativity which will constitute a significant contribution to knowledge of the interferon system. By successfully establishing an independent research program the candidiate will contribute to undergraduate and graduate education in molecular and cellular biology.